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- W2961503558 abstract "Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (>10 min) febrile seizures; febrile or afebrile status epilepticus (>30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children's hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9-57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26-14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93-12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24-9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07-7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy." @default.
- W2961503558 created "2019-07-23" @default.
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- W2961503558 date "2019-07-13" @default.
- W2961503558 modified "2023-10-11" @default.
- W2961503558 title "Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort" @default.
- W2961503558 cites W1039718725 @default.
- W2961503558 cites W1500569882 @default.
- W2961503558 cites W1508599984 @default.
- W2961503558 cites W1514224917 @default.
- W2961503558 cites W1558757561 @default.
- W2961503558 cites W1567755466 @default.
- W2961503558 cites W1571270758 @default.
- W2961503558 cites W1673813955 @default.
- W2961503558 cites W1742756123 @default.
- W2961503558 cites W1926532831 @default.
- W2961503558 cites W1967986271 @default.
- W2961503558 cites W1974809694 @default.
- W2961503558 cites W1983334701 @default.
- W2961503558 cites W1988595550 @default.
- W2961503558 cites W1992393728 @default.
- W2961503558 cites W1992787503 @default.
- W2961503558 cites W2008349652 @default.
- W2961503558 cites W2011278122 @default.
- W2961503558 cites W2026167706 @default.
- W2961503558 cites W2034163951 @default.
- W2961503558 cites W2045791079 @default.
- W2961503558 cites W2048186906 @default.
- W2961503558 cites W2054409917 @default.
- W2961503558 cites W2056828047 @default.
- W2961503558 cites W2064136918 @default.
- W2961503558 cites W2071335594 @default.
- W2961503558 cites W2071379242 @default.
- W2961503558 cites W2092007796 @default.
- W2961503558 cites W2101383744 @default.
- W2961503558 cites W2106277748 @default.
- W2961503558 cites W2112922820 @default.
- W2961503558 cites W2118612570 @default.
- W2961503558 cites W2128746826 @default.
- W2961503558 cites W2129406235 @default.
- W2961503558 cites W2133660627 @default.
- W2961503558 cites W2135893137 @default.
- W2961503558 cites W2137688970 @default.
- W2961503558 cites W2140806988 @default.
- W2961503558 cites W2140968331 @default.
- W2961503558 cites W2143497811 @default.
- W2961503558 cites W2147817553 @default.
- W2961503558 cites W2152390416 @default.
- W2961503558 cites W2157508298 @default.
- W2961503558 cites W2165800754 @default.
- W2961503558 cites W2213636741 @default.
- W2961503558 cites W2224270755 @default.
- W2961503558 cites W2227079180 @default.
- W2961503558 cites W2256016639 @default.
- W2961503558 cites W2261871889 @default.
- W2961503558 cites W2281890638 @default.
- W2961503558 cites W2302301648 @default.
- W2961503558 cites W2398625550 @default.
- W2961503558 cites W2460477481 @default.
- W2961503558 cites W2512232080 @default.
- W2961503558 cites W2515037702 @default.
- W2961503558 cites W2516639160 @default.
- W2961503558 cites W2550390537 @default.
- W2961503558 cites W2563036039 @default.
- W2961503558 cites W2576230061 @default.
- W2961503558 cites W2581021936 @default.
- W2961503558 cites W2592509339 @default.